: Although there has been evidence for a relationship between sickle cell disease (SCD) and pathology of the central nervous system (CNS) since 1923, there has been a tendency in the psychosocial literature to attribute any decreased cognitive performance in children with SCD to illness-related or demographic factors (e.g., school absenteeism, SES) rather than to the disease process of SCD (e.g., chronic microvascular insults to the CNS). Cerebral infarction is the most common neurological complication that occurs in children with SCD, but clinically it presents itself in only 5-10 percent of children with this chronic illness. Pertinent in this regard is the majority of children with SCD who are also at high risk of demonstrating learning deficits and poor school performance. Recent studies suggest that a significant number of children with SCD who do not display any overt symptomatology of neurologic disease often exhibit decreased academic performance in comparison to healthy matched peers. Given the pathophysiology of SCD, it is reasonable to hypothesize that the insidious onset of impaired cognitive functioning is the result of multiple microinfarcts, small hemorrhages, and progressive vascular disease. Therefore, the disease process of SCD could be a primary contributing factor to long-term decreased cognitive performance often demonstrated by the adult SCD population. It is thus critical to examine young children with SCD who do not exhibit gross manifestations of neurological insult in order to determine the cause of these cognitive deficits. The overall purpose of this proposal is to identify those factors that contribute to cognitive deficiencies associated with children with SCD who have not demonstrated any overt or clinically apparent neurological abnormalities. Specifically, 60 infants and toddlers with SCD and 60 matched normally developing peers between the ages of birth and 3 years will serve as subjects in a 5-year longitudinal design in order to permit between-group comparisons. Subjects will be assessed at regularly scheduled intervals with a variety of developmental (e.g., Bayley), cognitive (e.g., Stanford-Binet), neuropsychological (e.g., Purdue Pegboard), family functioning, and physiological indices in order to delineate those factors in the SCD group that are associated with decreased cognitive and academic performance. A unique and important feature of this research is the inclusion of MRI technology. These techniques make it possible to study in a comprehensive and componential manner the neuroanatomical effects of SCD instead of relying on any single instrument or assessment to document this phenomenon. Goals of this study include the identification of: (a) specific areas of learning deficiencies in children with SCD; (b) the period in which these deficiencies begin to occur; and (c) the relationship between types of learning deficits and various outcome measures. In sum, this study will determine how these factors interact and change over time as the child with SCD matures, the disease fluctuates, and the family and/or the environmental context changes in relation to cognitive development.